Early diagnostic markers for male systemic lupus erythematosus and related products and uses

Abstract

The present invention discloses markers for the early diagnosis of male systemic lupus erythematosus and related products and uses thereof. The markers include IL11RA, STARD8, PTGDS and / or S100A9. The present invention has verified that the markers have high accuracy, sensitivity and specificity in the diagnosis of early male systemic lupus erythematosus. By detecting the content of the markers in the blood, early and effective diagnosis of male systemic lupus erythematosus can be achieved. The present invention provides new ideas for the study of the pathogenesis of male systemic lupus erythematosus, and also provides a new target for the early diagnosis of male systemic lupus erythematosus.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine technology, and specifically relates to early diagnostic markers for male systemic lupus erythematosus and related products and uses. More specifically, the markers include IL11RA, STARD8, PTGDS and / or S100A9. Background Art

[0002] Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a wide range of clinical symptoms, with a slow, insidious onset, primarily affecting young women. SLE can affect multiple organs, with clinical manifestations ranging from mild fatigue and rash to severe, life-threatening organ damage, such as hematologic abnormalities, renal impairment, and neuropsychiatric changes. A key characteristic of SLE epidemiology is that, while SLE can affect men of any age, women predominate. Accumulated data in the medical literature indicate that male SLE patients comprise 4% to 22% of all SLE patients. However, in familial cluster studies, male SLE patients comprise 30%. Although the incidence of SLE in men is not as high as in women, studies have shown that male SLE patients experience more severe sequelae than female SLE patients. For example, previous studies have reported significantly higher rates of skin involvement, hematologic involvement, myocardial infarction, and renal involvement in male SLE patients compared with female SLE patients. Therefore, in the context of the poor prognosis of male SLE patients, revealing the potential molecular characteristics and mechanisms of male SLE is of great significance for discovering reliable biomarkers that can be used for accurate diagnosis and effective treatment of male SLE and for evaluating its prognosis.

[0003] While the pathogenesis of SLE remains uncertain, most studies suggest it is related to a combination of genetics, environment, immune dysfunction, and sex hormones. The development of SLE occurs through a breakdown of the immune system's own tolerance, a process often involving various inflammatory mediators, with the production of autoantibodies by immune dysfunction being the most important factor. The involvement of multiple autoantibodies at various stages of SLE contributes to its complex clinical presentation, variable course, and multi-organ system involvement. Some scholars speculate that this may be related to sex hormone levels. Furthermore, literature has reported that testosterone and dehydroepiandrosterone levels are lower in male SLE patients compared to healthy men, and low testosterone is considered a possible independent risk factor for the development of lupus nephritis (LN).

[0004] With the rapid development of microarray technology, those skilled in the art can use microarrays to detect differentially expressed genes (DEGs) between different populations. Microarray technology can display expressed genes and identify the specific proteins produced by genes. Therefore, these tools can be used to identify disease-related molecules. Currently, a large number of bioinformatics studies are focused on the DEGs between SLE patients and healthy controls. IFI27, IFI44L, IFIT1, and IFIT3 have been identified as hub genes involved in the pathogenesis of SLE. In addition, recent research has led to an increasing understanding that genetic factors play a decisive role in the pathogenesis of SLE. The genes that cause SLE are not single genes but rather multiple genes that initiate the development of the disease in a cascade or interactive manner. Although numerous studies have identified many promising biomarkers for the diagnosis of SLE, to date, no biomarker is effective and accurate in diagnosing SLE. As a result, many SLE cases are diagnosed only after tissue damage occurs, delaying the optimal time for diagnosis and treatment. Furthermore, research on SLE in men is currently very limited, and studies on specific diagnostic markers for SLE in men are even rarer.

[0005] Due to the low incidence and small number of cases in male SLE, there are relatively few relevant literature reports both domestically and internationally. Furthermore, the few reports that exist lack clear conclusions regarding its incidence, clinical manifestations, degree of organ damage, efficacy, and prognosis. Furthermore, due to the atypical clinical presentation of SLE in men, laboratory results are easily affected by other immune disorders, resulting in false-positive or false-negative results, leading to a high rate of missed and misdiagnoses in clinical practice. However, there is currently no effective and accurate method for the early diagnosis of SLE in men, and there are no reports on the role of IL11RA, STARD8, PTGDS, and / or S100A9 in the early diagnosis of SLE in men. Summary of the Invention

[0006] The purpose of the present invention is to provide an early diagnostic marker for male systemic lupus erythematosus and related products and uses thereof, so as to solve the technical problems existing in the prior art such as missed diagnosis and high misdiagnosis rate of male systemic lupus erythematosus in laboratory testing.

[0007] The above-mentioned purpose of the present invention is achieved through the following technical solutions:

[0008] A first aspect of the present invention provides use of a reagent for detecting the expression level of IL11RA, STARD8, PTGDS and / or S100A9 in a sample in the preparation of a product for early diagnosis and / or prediction of male systemic lupus erythematosus.

[0009] Furthermore, the reagents include reagents for detecting the expression level of IL11RA, STARD8, PTGDS and / or S100A9 mRNA in a sample, and reagents for detecting the expression level of IL11RA, STARD8, PTGDS and / or S100A9 protein in a sample.

[0010] Furthermore, the reagent is selected from the following group:

[0011] (1) Primers that specifically amplify IL11RA, STARD8, PTGDS, and / or S100A9;

[0012] (2) probes that specifically recognize IL11RA, STARD8, PTGDS, and / or S100A9;

[0013] (3) a binding agent that specifically binds to the protein encoded by IL11RA, STARD8, PTGDS, and / or S100A9;

[0014] Preferably, the sequences of the primers for specifically amplifying IL11RA, STARD8, PTGDS and / or S100A9 are shown as SEQ ID NO:5-SEQ ID NO:6, SEQ ID NO:7-SEQ ID NO:8, SEQ ID NO:3-SEQ ID NO:4 and / or SEQ ID NO:9-SEQ ID NO:10, respectively;

[0015] Preferably, the binding agent that specifically binds to the protein encoded by IL11RA, STARD8, PTGDS and / or S100A9 includes an antibody, a functional fragment of an antibody, or a conjugated antibody that specifically binds to the protein encoded by IL11RA, STARD8, PTGDS and / or S100A9.

[0016] Furthermore, the sample is selected from blood or tissue;

[0017] Preferably, the sample is selected from blood.

[0018] Furthermore, the probe that specifically recognizes IL11RA, STARD8, PTGDS and / or S100A9 can be DNA, RNA, DNA-RNA chimera, PNA or other derivatives. There is no limit to the length of the probe, as long as it completes specific hybridization and specifically binds to the target nucleotide sequence, any length is acceptable. The length of the probe can be as short as 25, 20, 15, 13 or 10 bases in length. Similarly, the length of the probe can be as long as 60, 80, 100, 150, 300 base pairs or longer, or even the entire gene. Since different probe lengths have different effects on hybridization efficiency and signal specificity, the length of the probe is usually at least 14 base pairs, and the longest generally does not exceed 30 base pairs. The length complementary to the target nucleotide sequence is optimally 15-25 base pairs. The probe's own complementary sequence is preferably less than 4 base pairs to avoid affecting hybridization efficiency;

[0019] Preferably, the probes include hybridization probes and hydrolysis probes (Taqman probes);

[0020] More preferably, both ends of the probe are connected to a quencher group and / or a fluorescent group;

[0021] Most preferably, the quenching group includes (but is not limited to): BHQ-0, BHQ-1, BHQ-2, BHQ-3, 3'-BBQ-650, Atto 540Q, Atto 575Q, Atto 612Q;

[0022] Most preferably, the fluorescent group includes (but is not limited to): FAM (carboxyfluorescein, green fluorescence), FITC (fluorescein isothiocyanate), TET (tetrachloro-6-carboxyfluorescein), HEX (hexachloro-6-methylfluorescein), JOE (2,7-dimethyl-4,5-dichloro-6-carboxyfluorescein), rhodamine (Rhodamine dyes such as R110, TAMRA, Texas Red, etc.), ROX, AlexaFluor dyes, ATTO dyes, DyLight dyes, cyanine dyes (such as Cy2, Cy3, Cy3.5, Cy3b, Cy5, Cy5.5, Cy7, Cy7.5), FluoProbes dyes, SulfoCy dyes, Seta dyes, IRIS dyes, SeTau dyes, SRfluor dyes, Square dyes.

[0023] In some embodiments, the present invention provides the use of a reagent for detecting the expression level of IL11RA, STARD8, PTGDS and / or S100A9 in a sample in the preparation of a product for early diagnosis and / or prediction of male systemic lupus erythematosus, wherein the IL11RA (Interleukin 11 receptor subunit alpha, Gene ID: 3590), STARD8 (StARrelated lipid transfer domain containing 8, Gene ID: 9754), PTGDS (ProstaglandinD2 synthase, Gene ID: 5730), and S100A9 (S100 calcium binding protein A9, Gene ID: 6280) include genes and proteins encoded thereby, and homologs, mutations, and isoforms thereof. The IL11RA, STARD8, PTGDS and / or S100A9 encompass full-length, unprocessed IL11RA, STARD8, PTGDS and / or S100A9, as well as any form of IL11RA, STARD8, PTGDS and / or S100A9 derived from processing in cells, and also encompass naturally occurring variants of IL11RA, STARD8, PTGDS and / or S100A9 (e.g., splice variants or allelic variants). Gene IDs can be obtained at https: / / www.ncbi.nlm.nih.gov / gene / .

[0024] In a preferred embodiment, the present invention provides use of a reagent for detecting the expression level of IL11RA in a sample in the preparation of a product for early diagnosis and / or prediction of male systemic lupus erythematosus.

[0025] In another preferred embodiment, the present invention provides use of a reagent for detecting the expression level of STARD8 in a sample in the preparation of a product for early diagnosis and / or prediction of male systemic lupus erythematosus.

[0026] In another preferred embodiment, the present invention provides use of a reagent for detecting the expression level of PTGDS in a sample in the preparation of a product for early diagnosis and / or prediction of male systemic lupus erythematosus.

[0027] In another preferred embodiment, the present invention provides use of a reagent for detecting the expression level of S100A9 in a sample in the preparation of a product for early diagnosis and / or prediction of male systemic lupus erythematosus.

[0028] In another preferred embodiment, the present invention provides use of a reagent for detecting the expression levels of IL11RA and STARD8 in a sample in the preparation of a product for early diagnosis and / or prediction of male systemic lupus erythematosus.

[0029] In another preferred embodiment, the present invention provides use of a reagent for detecting the expression levels of IL11RA and PTGDS in a sample in the preparation of a product for early diagnosis and / or prediction of male systemic lupus erythematosus.

[0030] In another preferred embodiment, the present invention provides use of a reagent for detecting the expression levels of IL11RA and S100A9 in a sample in the preparation of a product for early diagnosis and / or prediction of male systemic lupus erythematosus.

[0031] In another preferred embodiment, the present invention provides use of a reagent for detecting the expression levels of STARD8 and PTGDS in a sample in the preparation of a product for early diagnosis and / or prediction of male systemic lupus erythematosus.

[0032] In another preferred embodiment, the present invention provides use of a reagent for detecting the expression levels of STARD8 and S100A9 in a sample in the preparation of a product for early diagnosis and / or prediction of male systemic lupus erythematosus.

[0033] In another preferred embodiment, the present invention provides use of a reagent for detecting the expression levels of PTGDS and S100A9 in a sample in the preparation of a product for early diagnosis and / or prediction of male systemic lupus erythematosus.

[0034] In another preferred embodiment, the present invention provides use of a reagent for detecting the expression levels of IL11RA, STARD8, and PTGDS in a sample in the preparation of a product for early diagnosis and / or prediction of male systemic lupus erythematosus.

[0035] In another preferred embodiment, the present invention provides use of a reagent for detecting the expression levels of IL11RA, STARD8, and S100A9 in a sample in the preparation of a product for early diagnosis and / or prediction of male systemic lupus erythematosus.

[0036] In another preferred embodiment, the present invention provides use of a reagent for detecting the expression levels of STARD8, PTGDS, and S100A9 in a sample in the preparation of a product for early diagnosis and / or prediction of male systemic lupus erythematosus.

[0037] In another preferred embodiment, the present invention provides use of a reagent for detecting the expression levels of IL11RA, STARD8, PTGDS, and S100A9 in a sample in the preparation of a product for early diagnosis and / or prediction of male systemic lupus erythematosus.

[0038] A second aspect of the present invention provides a product for early diagnosis and / or prognosis of male systemic lupus erythematosus.

[0039] Further, the product includes reagents for detecting the expression levels of IL11RA, STARD8, PTGDS, and / or S100A9 in a sample;

[0040] Preferably, the reagents include reagents for detecting the expression levels of IL11RA, STARD8, PTGDS and / or S100A9 in a sample by sequencing technology, nucleic acid hybridization technology, nucleic acid amplification technology, or protein immunoassay technology;

[0041] More preferably, the agent is selected from the following group:

[0042] (1) Primers that specifically amplify IL11RA, STARD8, PTGDS, and / or S100A9;

[0043] (2) probes that specifically recognize IL11RA, STARD8, PTGDS, and / or S100A9;

[0044] (3) a binding agent that specifically binds to the protein encoded by IL11RA, STARD8, PTGDS, and / or S100A9;

[0045] Preferably, the product includes a test kit, a chip, and a test paper;

[0046] Preferably, the sample is selected from blood or tissue;

[0047] More preferably, the sample is selected from blood.

[0048] Furthermore, the kit further comprises an auxiliary detection reagent for mRNA expression level, an auxiliary detection reagent for protein expression level, an auxiliary detection instrument for mRNA expression level and / or an auxiliary detection instrument for protein expression level;

[0049] Preferably, the auxiliary detection reagents for mRNA expression levels include (but are not limited to): reaction reagents for visualizing the amplicons corresponding to the primers, such as reagents for visualizing the amplicons by agarose gel electrophoresis, enzyme-linked gel electrophoresis, chemiluminescence, in situ hybridization, fluorescence detection, etc., RNA extraction reagents, reverse transcription reagents, cDNA amplification reagents, standards for preparing standard curves, positive controls, and negative controls;

[0050] Preferably, the auxiliary detection reagents for protein expression levels include (but are not limited to): blocking solution, antibody diluent, washing buffer, color development stop solution, and standards for preparing standard curves.

[0051] Furthermore, the chip includes a solid phase carrier and a reagent immobilized on the solid phase carrier for detecting the expression level of IL11RA, STARD8, PTGDS and / or S100A9 in a sample;

[0052] Preferably, the reagents include primers, oligonucleotide probes or chips targeting the IL11RA, STARD8, PTGDS and / or S100A9, and binding agents that specifically bind to proteins encoded by IL11RA, STARD8, PTGDS and / or S100A9;

[0053] More preferably, the binding agent includes an antibody, a functional fragment of an antibody, or a conjugated antibody that specifically binds to a protein encoded by IL11RA, STARD8, PTGDS, and / or S100A9.

[0054] Most preferably, the binding agent is an antibody that specifically binds to a protein encoded by IL11RA, STARD8, PTGDS and / or S100A9.

[0055] A third aspect of the present invention provides a diagnostic prediction model for early diagnosis and / or prediction of male systemic lupus erythematosus.

[0056] Furthermore, the diagnostic prediction model includes the following markers: IL11RA, STARD8, PTGDS, and S100A9;

[0057] Preferably, the diagnostic prediction model uses the following regression equation to calculate the diagnostic model prediction value:

[0058] Diagnostic model predicted value = 24.8812 + 1.6948 * PTGDS + 1.0869 * IL11RA - 2.2141 * STARD8 - 2.467 * S100A9;

[0059] Wherein, PTGDS, IL11RA, STARD8, and S100A9 represent the expression levels of PTGDS, IL11RA, STARD8, and S100A9 in the blood sample of the test subject;

[0060] More preferably, when the diagnostic model prediction value is ≤-0.195, the subject is judged to be a non-male systemic lupus erythematosus patient; when the diagnostic model prediction value is >-0.195, the subject is judged to be a male systemic lupus erythematosus patient or has a high risk of developing male systemic lupus erythematosus.

[0061] A fourth aspect of the present invention provides a system or device for early diagnosis and / or prognosis of male systemic lupus erythematosus.

[0062] Furthermore, the system or device includes:

[0063] (1) a data acquisition module for acquiring expression profile data of IL11RA, STARD8, PTGDS, and S100A9 in samples of test subjects;

[0064] (2) a diagnosis prediction module, configured to provide the expression profile data of IL11RA, STARD8, PTGDS, and S100A9 obtained by the data acquisition module as input data to a trained diagnosis prediction model, wherein the diagnosis prediction model is trained to perform a diagnosis prediction on the subject based on the expression profile data;

[0065] (3) a diagnosis prediction result acquisition module, used to obtain the output result of the diagnosis prediction model in the diagnosis prediction module to obtain the diagnosis prediction result of the subject;

[0066] Preferably, the diagnostic prediction model is the diagnostic prediction model described in the third aspect of the present invention;

[0067] More preferably, when the diagnostic model prediction value is ≤-0.195, the subject is judged to be a non-male systemic lupus erythematosus patient; when the diagnostic model prediction value is >-0.195, the subject is judged to be a male systemic lupus erythematosus patient or has a high risk of developing male systemic lupus erythematosus.

[0068] A fifth aspect of the present invention provides a computer-readable storage medium.

[0069] Furthermore, the computer-readable storage medium includes a stored computer program, and when the program is executed, the following method is implemented:

[0070] Obtaining expression profile data of IL11RA, STARD8, PTGDS, and S100A9 in samples from test subjects;

[0071] providing the expression profile data of IL11RA, STARD8, PTGDS and S100A9 obtained by the data acquisition module as input data to the diagnosis prediction model;

[0072] Outputting the subject's diagnostic prediction results;

[0073] Preferably, the diagnostic prediction model is the diagnostic prediction model described in the third aspect of the present invention;

[0074] More preferably, when the diagnostic model prediction value is ≤-0.195, the subject is judged to be a non-male systemic lupus erythematosus patient; when the diagnostic model prediction value is >-0.195, the subject is judged to be a male systemic lupus erythematosus patient or has a high risk of developing male systemic lupus erythematosus.

[0075] A sixth aspect of the present invention provides an in vitro screening method for candidate drugs for treating male systemic lupus erythematosus.

[0076] Furthermore, the method comprises the following steps:

[0077] (1) Adding the drug to be tested to a system expressing or containing IL11RA, STARD8, PTGDS, and / or S100A9;

[0078] (2) detecting the expression levels of IL11RA, STARD8, PTGDS, and / or S100A9 in the system;

[0079] (3) Select drugs that can significantly increase the expression level of IL11RA and / or PTGDS and significantly reduce the expression level of STARD8 and / or S100A9 as candidate drugs.

[0080] Furthermore, the drugs to be tested include but are not limited to: reagents and small molecule compounds designed to promote the expression of one or more of IL11RA and PTGDS genes or their upstream or downstream genes; reagents and small molecule compounds designed to inhibit the expression of one or more of STARD8 and S100A9 genes or their upstream or downstream genes.

[0081] Furthermore, the system is selected from: a cell system, a subcellular system, a solution system, a tissue system, an organ system or an animal system.

[0082] A seventh aspect of the present invention provides an application of any of the following aspects:

[0083] (1) Use of reagents for detecting the expression levels of IL11RA, STARD8, PTGDS, and / or S100A9 in constructing a system or device for early diagnosis and / or prediction of systemic lupus erythematosus in men;

[0084] (2) Use of a reagent for detecting the expression level of IL11RA, STARD8, PTGDS, and / or S100A9 in constructing a computer-readable storage medium;

[0085] (3) Use of reagents for detecting the expression levels of IL11RA, STARD8, PTGDS, and / or S100A9 in in vitro screening of drug candidates for the treatment of systemic lupus erythematosus in men;

[0086] (4) Use of an agent that promotes the expression of IL11RA and / or PTGDS, or an agent that inhibits the expression of STARD8 and / or S100A9, in the preparation of a drug for treating male systemic lupus erythematosus.

[0087] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0088] The present invention first discovered that IL11RA, STARD8, PTGDS and / or S100A9 were significantly differentially expressed between blood samples of male systemic lupus erythematosus patients and healthy controls, and verified that any one or more combinations of IL11RA, STARD8, PTGDS and / or S100A9 can be used for the accurate and effective diagnosis of male systemic lupus erythematosus. In particular, the AUC value of the combination of IL11RA, STARD8, PTGDS and S100A9 was as high as 0.940, with sensitivity and specificity both exceeding 84%, showing high diagnostic accuracy, sensitivity and specificity. Based on this, tools and products for the early diagnosis of male systemic lupus erythematosus can be developed, which is of great significance for guiding the prevention and screening of high-risk groups of male systemic lupus erythematosus, and provides a basis for earlier and more effective intervention in male systemic lupus erythematosus and improving patient prognosis. In addition, the present invention provides guidance for experimental research and clinical transformation related to male systemic lupus erythematosus. BRIEF DESCRIPTION OF THE DRAWINGS

[0089] Figure 1 The results of differential expression of PTGDS, IL11RA, STARD8 and S100A9 between blood samples of male systemic lupus erythematosus patients (SLE) and male healthy controls (HC) collected in Hainan Provincial People's Hospital, among which, Figure A: PTGDS, Figure B: IL11RA, Figure C: STARD8, Figure D: S100A9, *P<0.05, **P<0.01, ***P<0.001;

[0090] Figure 2 The figure shows the comparison results of PTGDS, IL11RA, STARD8 and S100A9 levels in male systemic lupus erythematosus (SLE) patients and male healthy controls (HC) in the test set (GSE49454), where *P<0.05, **P<0.01, ***P<0.001;

[0091] Figure 3These are the result graphs related to GO enrichment analysis and KEGG enrichment analysis, among which, Figure A: enrichment bar graph for visualization of GO and KEGG enrichment analysis, Figure B: enrichment chord graph for visualization of GO and KEGG enrichment analysis, Figure C: enrichment circle graph for visualization of GO and KEGG enrichment analysis;

[0092] Figure 4 Figure 2 shows the comparison of PTGDS, IL11RA, STARD8, and S100A9 levels in male systemic lupus erythematosus (SLE) patients and male healthy controls (HC) in the validation set (GSE65391+GSE49454). *P<0.05, **P<0.01, ***P<0.001.

[0093] Figure 5 The ROC curve results show the diagnostic efficacy of PTGDS, IL11RA, STARD8 and / or S100A9 single detection indicators and combined detection diagnostic model for male systemic lupus erythematosus in the validation set (GSE65391+GSE49454). Among them, model (Combination model) represents the diagnostic prediction model obtained by combining the four indicators PTGDS, IL11RA, STARD8 and S100A9. DETAILED DESCRIPTION

[0094] The present invention will be further described below in conjunction with specific examples, which are intended only to explain the present invention and are not to be construed as limiting the present invention. Those skilled in the art will appreciate that various changes, modifications, substitutions, and variations may be made to these examples without departing from the principles and aims of the present invention, and that the scope of the present invention is defined by the claims and their equivalents. The experimental methods in the following examples, for which specific conditions are not specified, are generally tested under conventional conditions or under conditions recommended by the manufacturer.

[0095] Unless otherwise defined, all technical terms in the context of the present invention have the same meanings as understood by those of ordinary skill in the art. In addition, some terms are explained as follows.

[0096] The markers for early diagnosis and / or prediction of male systemic lupus erythematosus described herein include IL11RA (Interleukin 11 receptor subunit alpha, Gene ID: 3590), STARD8 (StAR related lipid transfer domain containing 8, Gene ID: 9754), PTGDS (Prostaglandin D2 synthase, Gene ID: 5730), and S100A9 (S100 calcium binding protein A9, Gene ID: 6280). The markers for early diagnosis and / or prediction of male systemic lupus erythematosus are preferably a combination of IL11RA, STARD8, PTGDS, and S100A9. Verification has found that the AUC value of the combination is as high as 0.940, and the sensitivity and specificity are both higher than 84%. The combination has high diagnostic accuracy, sensitivity, and specificity, and can be used for the early and accurate diagnosis of male systemic lupus erythematosus.

[0097] The term "IL11RA, STARD8, PTGDS and / or S100A9" as used herein refers to any one or more combinations of IL11RA, STARD8, PTGDS and / or S100A9, including the following technical solutions: (1) IL11RA, (2) STARD8, (3) PTGDS, (4) S100A9, (5) a combination of IL11RA and STARD8, (6) a combination of IL11RA and PTGDS, (7) a combination of IL11RA and S100A9, (8) a combination of STARD8 and PTGDS (9) STARD8 and S100A9 are combined, (10) PTGDS and S100A9 are combined, (11) IL11RA, STARD8 and PTGDS are combined, (12) IL11RA, STARD8 and S100A9 are combined, (13) STARD8, PTGDS and S100A9 are combined, (14) IL11RA, STARD8, PTGDS and S100A9 are combined. In a specific embodiment of the present invention, IL11RA, STARD8, PTGDS and S100A9 are preferably combined.

[0098] As used herein, the terms "early diagnosis" and "diagnosis" refer to the identification or classification of a molecular or pathological state, disease or condition. For example, "diagnosis" can refer to identifying the risk of male systemic lupus erythematosus by the tissue / organ involved (e.g., male systemic lupus erythematosus), or by molecular characteristics (e.g., characterized by the expression of one or a combination of a specific gene or the protein encoded by the gene). The term "diagnosis and / or prediction" includes determining whether a subject suffers from male systemic lupus erythematosus and determining the risk of a subject suffering from male systemic lupus erythematosus. As is well known to those skilled in the art, the step of associating biomarker levels with a certain probability or risk can be implemented in different ways. Preferably, the measured concentrations of the protein and one or more other markers are mathematically combined, and the combined value is associated with the underlying diagnostic problem. The determination of marker values ​​can be combined by any suitable prior art mathematical method.

[0099] The term "expression level" as used herein refers to the amount of polynucleotides or amino acid products or proteins in a biological sample. Expression generally refers to the process in which the information encoded by a gene is converted into a structure that exists and operates in a cell. Therefore, the "expression" of a biomarker used herein refers to transcription into polynucleotides, translation into proteins or even post-translational modification of proteins. Fragments of transcribed polynucleotides, translated proteins or post-translationally modified proteins are also considered to be expressed, whether they are derived from transcripts produced by alternative splicing or degraded transcripts, or from post-translational processing of proteins (e.g., by proteolysis). Expressed genes include those that are transcribed into polynucleotides (e.g., mRNA) and then translated into proteins, and those that are transcribed into RNA but not translated into proteins (e.g., transfer RNA and ribosomal RNA).

[0100] As used herein, the term "differential expression" refers to a difference in the expression level of one or more biomarkers compared to the expression level of the same biomarker in a second sample. Differential expression can be determined as described herein and by methods well known to those skilled in the art. The term "differential expression" or "change in expression level" means an increase or decrease in the measurable expression level of a given biomarker in a sample, as compared to the measurable expression level of a given biomarker in a second sample, as determined by measuring the amount of RNA. The term "differential expression" or "change in expression level" can also mean an increase or decrease in the measurable expression level of a given biomarker in a sample population, as compared to the measurable expression level of a biomarker in a second sample population.

[0101] As used herein, the term "primer" refers to a 7-50 nucleic acid sequence that can form a base pair complementary to a template strand and acts as a starting point for replicating the template strand. Primers are typically synthesized, but naturally occurring nucleic acids may also be used. The sequence of the primer does not necessarily need to be identical to that of the template, as long as it is sufficiently complementary and capable of hybridizing with the template. Additional features that do not change the basic properties of the primer may be mixed in. Examples of additional features that may be mixed in include methylation, capping, replacement of one or more nucleic acids by homologs, and modification between nucleic acids, but are not limited thereto. In a specific embodiment of the present invention, the sequences of primers for IL11RA, STARD8, PTGDS, and / or S100A9 are preferably primers as shown in SEQ ID NO: 5-SEQ ID NO: 6, SEQ ID NO: 7-SEQ ID NO: 8, SEQ ID NO: 3-SEQ ID NO: 4, and / or SEQ ID NO: 9-SEQ ID NO: 10.

[0102] The term "antibody" as used herein refers to a substance that specifically binds to an antigen to cause an antigen-antibody reaction. For the purposes of the present invention, an antibody refers to an antibody that specifically binds to the markers for early diagnosis of male systemic lupus erythematosus (IL11RA, STARD8, PTGDS and / or S100A9) of the present invention. The antibodies of the present invention include polyclonal antibodies, monoclonal antibodies and recombinant antibodies. The above antibodies can be easily prepared using techniques well known in the art. For example, polyclonal antibodies can be produced according to methods well known in the art by a process including injecting the above marker protein antigen into an animal and collecting blood from the animal to obtain serum containing the antibody. Such polyclonal antibodies can be prepared from any animal such as goats, rabbits, sheep, monkeys, horses, pigs, cattle, dogs, etc. In addition, monoclonal antibodies can be prepared using hybridoma methods or phage antibody library technology well known in the art. The antibodies prepared by the above methods can be separated and purified using methods such as gel electrophoresis, dialysis, salt precipitation, ion exchange chromatography, affinity chromatography, etc. Furthermore, the antibodies of the present invention include not only intact forms comprising two full-length light chains and two full-length heavy chains, but also functional fragments of antibody molecules. Functional fragments of antibody molecules refer to fragments that have at least antigen-binding function, including Fab, F(ab'), F(ab')2, and Fv. Furthermore, the antibodies of the present invention are commercially available.

[0103] As used herein, the term "sample" refers to a composition obtained or derived from a subject (e.g., an individual of interest) that contains cells and / or other molecular entities to be characterized and / or identified based on, for example, physical, biochemical, chemical, and / or physiological characteristics. For example, a sample refers to any sample derived from a subject of interest that is expected or known to contain cells and / or molecular entities to be characterized. Samples include, but are not limited to, tissue samples, primary or cultured cells or cell lines, cell supernatants, cell lysates, platelets, serum, plasma, vitreous humor, lymphatic fluid, synovial fluid, follicular fluid, semen, amniotic fluid, milk, whole blood, blood-derived cells, urine, cerebrospinal fluid, saliva, sputum, tears, sweat, mucus, tissue culture fluid, tissue extracts, homogenized tissue, tumor tissue, cell extracts, and combinations thereof. In a specific embodiment of the present invention, the sample is preferably a blood sample from a subject.

[0104] The term "AUC" or "AUC value" used herein refers to the area under the receiver operating characteristic curve, which refers to a graphical curve showing the variation of the performance of a binary classifier system along with its discrimination threshold. This curve is created by drawing a curve of the true positive rate to the false positive rate under various threshold settings. The true positive rate is also referred to as sensitivity. The false positive rate is calculated as 1-specificity. Therefore, the ROC curve is a graphical display of the true positive rate to the false positive rate (sensitivity vs (1-specificity)) within a series of cutoff values ​​and the mode of selecting the best cutoff value for clinical use. Accuracy is expressed as the area under the ROC curve (AUC), which provides a useful parameter for comparing test performance. An AUC close to 1 indicates that the test is highly sensitive and has a high degree of specificity, while an AUC close to 0.5 indicates that the test is neither sensitive nor specific.

[0105] In the specific examples of the present invention, all experiments were repeated at least three times. The results are expressed as mean ± standard deviation. Statistical analysis was performed using SPSS statistical software. One-way ANOVA and Tukey S test were used for comparison between the two groups. P < 0.05 was considered statistically significant.

[0106] In order to overcome the technical problems in the field such as missed diagnosis and high misdiagnosis rate of laboratory testing for male systemic lupus erythematosus, the inventors of the present invention have identified for the first time markers that can be used for early and accurate diagnosis of male systemic lupus erythematosus, including any one or more of IL11RA, STARD8, PTGDS and / or S100A9. The markers can distinguish male systemic lupus erythematosus patients from non-male systemic lupus erythematosus patients with high diagnostic ability.

[0107] In one embodiment, at least one of IL11RA, STARD8, PTGDS and / or S100A9 is compared to a reference level of the corresponding gene. Such comparison enables determination of whether an individual has male systemic lupus erythematosus or a high or low risk of developing male systemic lupus erythematosus.

[0108] In a preferred embodiment, the reference level is measured by measuring a human serum albumin isolated from at least one subject (e.g., isolated from at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 100, 150, 200, 250, 300, 400, 500, or 45, 46, 47, 48, 49, 50, 100, 150, 200, 250, 300, 400, 500, or 1000 reference biological samples) compared to at least one reference biological sample (e.g., at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 100, 150, 200, 250, 300, 400, 500, or 1000 reference biological samples) of 1000 healthy subjects who do not have male systemic lupus erythematosus. The at least one subject who does not have male systemic lupus erythematosus can be considered a healthy subject relative to a male systemic lupus erythematosus patient.

[0109] In a preferred embodiment, compared with normal controls (reference levels), the expression levels of IL11RA and PTGDS in male patients with systemic lupus erythematosus are significantly downregulated, and the expression levels of STARD8 and S100A9 in male patients with systemic lupus erythematosus are significantly upregulated.

[0110] In a preferred embodiment, whether a subject suffers from male systemic lupus erythematosus or the risk of suffering from male systemic lupus erythematosus is determined by detecting the expression levels of IL11RA, STARD8, PTGDS and / or S100A9.

[0111] In the present invention, the sample includes (but is not limited to): tissue sample, blood sample (such as whole blood or blood components, such as blood cells / cell components, serum or plasma) sample, urine sample, aqueous humor or sample from other peripheral sources.

[0112] In a specific embodiment of the present invention, the sample is selected from blood derived from a subject.

[0113] The present invention will be further described in detail below with reference to the accompanying drawings and examples. The following examples are intended to illustrate the present invention only and are not intended to limit the scope of the invention. Experimental methods in the examples where specific conditions are not specified are generally carried out under conventional conditions or as recommended by the manufacturer.

[0114] Example 1 Real-time quantitative PCR detection of gene expression in clinical samples of male patients with systemic lupus erythematosus

[0115] 1. Clinical sample collection

[0116] The present invention collected blood samples from 5 male systemic lupus erythematosus (SLE) patients and 5 male normal subjects, and the blood samples of the 5 male SLE patients and 5 male normal subjects were collected from Hainan Provincial People's Hospital. All SLE patients met the latest ACR / EULAR classification and diagnostic criteria for systemic lupus erythematosus in 2019. The present invention collected laboratory data for each SLE patient, including white blood cell count, platelet, creatinine, lactate dehydrogenase, d-dimer, complement 3 and complement 4 levels. The basic clinical characteristics of male SLE patients recruited in this study are shown in Table 1. This study was approved by the Ethics Committee of Hainan Provincial People's Hospital. The subjects were informed of the experimental protocol and procedures and signed an informed consent form with them. The ethics approval number is Med-Eth-Re

[2022] 156.

[0117] The inclusion and exclusion criteria for male patients with systemic lupus erythematosus are as follows:

[0118] (1) Inclusion criteria: ① Age 18-65 years, limited to males; ② No treatment at the initial diagnosis or relapse more than 6 months after discontinuation of medication and no further treatment; ③ SLEDAI score > 10 points; ④ Meet the 2019 ACR / EULAR classification diagnostic criteria for systemic lupus erythematosus;

[0119] (2) Exclusion criteria: ① Those who cannot take care of themselves; ② Those who have had or are currently suffering from malignant tumors; ③ Those who have a history of chronic infection or a history of severe infection in the past 2 months; ④ Those who have uncontrolled diseases involving important organs.

[0120] Table 1 Basic clinical characteristics of male SLE patients recruited in this study

[0121]

[0122] 2. Experimental reagents

[0123] PCR primers were synthesized by Shanghai Bioengineering; Trizol (9109) (Takara, Japan); iScript cDNA synthesis kit (1708891EDU) (Bio-Rad, Hercules, CA, USA); SYBR Green Premix Ex Taq TM (RR420Q) (Takara, Japan); DNase I (EN0523), RNase-free (EN0523) (Thermo Fisher Scientific, Pittsburgh, PA, USA); diethyl pyrocarbonate (DEPC) (97062-650) (Amresco, Ohio, USA).

[0124] 3. Experimental instruments

[0125] FORMA 700 ultra-low temperature refrigerator, Thermo Fisher Scientific; YC-300L medicine storage cabinet, Zhongke Meiling Cryogenic Technology Co., Ltd.; Direct-Q with pump ultrapure water analyzer, Millipore Corporation; SW-CJ-2FD ultra-clean workbench, Suzhou Purification Equipment Co., Ltd.; 3K15 low-temperature high-speed centrifuge, Sigma; BS224 electronic balance, Beijing Sartorius Instrument System Co., Ltd.; ABI 7500 real-time fluorescence quantitative PCR instrument, Applied Biosystems (ABI), USA; Applied Biosystems Veriti 96-Well Thermal Cycler, Life Technology; Nanodrop 2000, Thermo Fisher Scientific.

[0126] 4. Experimental Grouping

[0127] Peripheral blood samples from male SLE patients served as the experimental group, while peripheral blood samples from normal subjects served as the control group. qPCR was used to detect differences in the expression levels of four genes: PTGDS, IL11RA, STARD8, and S100A9.

[0128] 5. qPCR experimental method

[0129] (1) Primer design

[0130] The primers used for real-time qPCR detection of the expression levels of genes PTGDS, IL11RA, STARD8, and S100A9 were synthesized by Shanghai Bioengineering. The specific primer sequences are shown in Table 2 below.

[0131] Table 2 Primer sequence information for real-time qPCR detection of genes PTGDS, IL11RA, STARD8, and S100A9

[0132]

[0133] (2) Extraction of mRNA from blood samples

[0134] According to the experimental group, 300 μL of the whole blood sample collected by the present invention was added to an EP tube, 500 μL of Trizol was added, vortexed and thoroughly mixed, and lysed at room temperature for 15 minutes to fully lyse the cells in the whole blood. Centrifuged at 4°C for 10 minutes, the supernatant was aspirated, and the liquid was transferred to another new 1.5 mL centrifuge tube that had been autoclaved. 100 μL of chloroform (1 / 5 of the volume of Trizol) was added and gently pipetted to mix. The tube was incubated at room temperature for 15 minutes, centrifuged at 12000 rpm at 4°C for 15 minutes, and the supernatant was removed (avoiding the middle layer). An equal amount of isopropanol, approximately 200 μL, was added, shaken vigorously, and allowed to stand at -20°C for 30 minutes to precipitate RNA. The tube was centrifuged at 12000 rpm at 4°C for 10 minutes, and the supernatant was discarded. 1 mL of 75% ethanol (prepared with DEPC water) was added for washing, centrifuged at 7500 rpm at 4°C for 5 minutes, the supernatant discarded, and allowed to dry naturally for 5-10 minutes. Dissolve RNA in 10 μL of DEPC water and mix thoroughly by pipetting to obtain a total RNA solution. Take 2 μL of sample and use Nanodrop 2000 to determine the mRNA concentration and purity.

[0135] (3) cDNA synthesis

[0136] cDNA synthesis was performed using a 20 μL system. To a 200 μL eppendorf tube, which had been previously enzyme-free, 2 μL of RNA, 4 μL of 5× iScript reaction mix, 1 μL of iScript reverse transcriptase, and 13 μL of nuclease-free water were added. The reaction was incubated at 25°C for 5 minutes, 42°C for 30 minutes, and 85°C for 5 minutes to obtain cDNA, which was then stored at -70°C.

[0137] (4) Real-time quantitative PCR detection

[0138] Using a 20 μL system, 1 μL of cDNA, 7.4 μL of nuclease-free water, 10 μL of Ssofast EvaGreen Supermix, 0.8 μL of forward primer, and 0.8 μL of reverse primer were added to a 200 μL eppendorf tube after enzyme removal. The premixed reagents were added to an 8-tube strip, sealed, and placed in the instrument. The reaction parameters were set and amplification was performed. The results were obtained using 2 -ΔΔCt The primers used were shown in Table 2.

[0139] The amplification program was as follows: 95°C×30 sec, (95°C×10 sec, 60°C×30 sec)×40 cycles, 95°C×15 sec, 60°C×60 sec, 95°C×15 sec.

[0140] 6. Data Analysis

[0141] The expression levels of blood samples collected from Hainan Provincial People's Hospital are expressed as mean ± standard deviation (mean ± SD). One-way ANOVA and Tukey S test were used to analyze the differences in gene expression levels in blood samples from male SLE patients and normal male subjects at Hainan Provincial People's Hospital. P < 0.05 was considered statistically significant.

[0142] 7. Experimental results

[0143] See the results Figure 1 A- Figure 1 D. The results showed that compared with normal male subjects, the expression levels of PTGDS, IL11RA, STARD8 and S100A9 in the blood samples of male SLE patients were significantly changed, and the differences were statistically significant (P<0.05). Among them, compared with normal male subjects, the expression level of PTGDS in the blood samples of male SLE patients was significantly downregulated, the expression level of IL11RA in the blood samples of male SLE patients was significantly downregulated, the expression level of STARD8 in the blood samples of male SLE patients was significantly upregulated, and the expression level of S100A9 in the blood samples of male SLE patients was significantly upregulated.

[0144] Example 2 Identification of key genes associated with male SLE, study of the pathogenesis of male SLE, and verification of the diagnostic efficacy of key genes

[0145] 1. Data download and preprocessing

[0146] Using the keyword "systemic lupus erythematosus," we searched for SLE expression profiles in the GEO database, a publicly available database. Studies meeting the following criteria were included: 1) whole-genome expression data for male and female SLE patients; 2) datasets containing complete sample information. We selected the dataset GSE49454 (GPL10558), which includes 26 male SLE samples and 3 male normal subjects, as the test set. We also selected the dataset GSE65391 (GPL10558), which includes 19 male SLE samples and 10 male normal subjects, and used it together with GSE49454 as the validation set.

[0147] The expression data of GSE49454 were analyzed. Differentially expressed genes (DEGs) between male SLE patients and male healthy controls were obtained using the online web tool GEO2R. An adjusted P value < 0.05 was used as the threshold.

[0148] 2. Functional enrichment analysis

[0149] GO and KEGG enrichment analysis of identified DEGs was performed using R packages (ClusterProfile, Ggplot2, and GOplot). The ClusterProfile package was used for DEG enrichment analysis. The results were visualized using Ggplot2 and GOplot packages.

[0150] 3. Data Analysis

[0151] Statistical analysis was performed using RStudio software and IBM SPSS Statistics 22 (SPSS, Inc., Chicago, IL, USA). Data were analyzed and plotted using Graphpad Prism 5 (5.01). Because the samples did not meet the normality test, the expression levels of the identified DEGs were tested using the Mann-Whitney u test using GSE65391 and GSE49454. The receiver operating characteristic curve (ROC-AUC) was used to compare the diagnostic efficacy of different DEGs and their combined models. P < 0.05 was considered statistically significant.

[0152] 4. Experimental results

[0153] (1) Analysis of DEGs and their biological functions in male SLE patients (SLE) and male healthy controls (HC)

[0154] After normalization of the chip results in the test set GSE49454, 7 DEGs were identified, among which keratin 72 (KRT72), prostaglandin D2 synthase (PTGDS), interleukin 11 receptor subunit α (IL11RA), and LOC732134 were downregulated; the other 3 DEGs, including dmrt-like C2 family (DMRTC2), Star-associated lipid transfer domain containing 8 (STARD8), and S100 calcium-binding protein A9 (S100A9), were upregulated (see Figure 2 ). GO and KEGG enrichment analysis were used to analyze the 7 DEGs identified above. Based on GO enrichment, biological processes were significantly enriched in the cyclooxygenase pathway, positive regulation of histone H3-K9 methylation, and regulation of histone H3-K9 trimethylation. These proteins are mainly distributed on the XY body and sex chromosomes. In terms of molecular function, these proteins play a role in fatty acid binding, monocarboxylic acid binding, and carboxylic acid binding. At the same time, KEGG pathway analysis showed that these proteins are involved in arachidonic acid metabolism, IL-17 signaling pathway, and hematopoietic cell lineage (see Figure 3 A- Figure 3 C).

[0155] PTGDS catalyzes the conversion of prostaglandin H2 (PGH2) to prostaglandin D2 (PGD2). PGD2 functions as a neuromodulator and trophic factor in the central nervous system. This gene is preferentially expressed in the brain. Previous studies have shown that male patients have a higher incidence of epileptic seizures and neuropsychiatric disorders than female patients. The results of this study show that PTGDS is significantly decreased in male patients, which may explain the higher degree of neurological involvement in male patients. IL-11 is a member of the IL-6 family of cytokines, and IL11RA is its receptor subunit. IL-11's biological responses are induced through the JAK / STAT signaling pathway. IL-11, IL-13, and IL-4 can increase the frequency of macrophage differentiation from myeloid progenitor cells. Previous studies have shown that IL-11 promotes a fibrotic phenotype. IL-11 was previously considered a pathogenic factor, with elevated IL-11 levels found in a range of disease states, including cardiac, renal, and skin fibrosis, as well as rheumatoid arthritis. Furthermore, this study found that IL11RA expression was significantly decreased in male SLE patients, suggesting that IL11RA may have a protective role in male SLE. STARD8, located on the X chromosome, encodes a member of the RhoGTPase activating protein subfamily. This protein contains a steroidogenic acute regulatory protein-related lipid transfer domain. The STARD8 gene may play a role in male primary gonadal and testosterone synthesis. Therefore, STARD8 is important in sexual development. This study found that STARD8 expression levels were significantly elevated in male SLE patients, suggesting that elevated STARD8 levels in males may be associated with a higher incidence of SLE. S100A9, a member of the calcium-binding S100 protein family, is released by phagocytes at sites of inflammation. This study found that S100A9 expression levels were significantly elevated in male SLE patients. Further studies are needed to evaluate the therapeutic effects of S100A9 in SLE. Studying the responses of males and females will provide important theoretical foundations for SLE treatment, clarifying whether such treatments are equally effective in both sexes. In addition, this study predicted the target miRNAs and ncRNAs of PTGDS, IL11RA, STARD8, and S100A9, and constructed a ceRNA network using Cytoscape. The constructed ceRNA network revealed the mechanism by which the selected genes were regulated at the transcriptome level.

[0156] (2) GSE65391, GSE49454, and blood samples collected from Hainan Provincial People's Hospital were used to verify the expression of identified DEGs

[0157] The expression of the 7 identified DEGs was verified using the validation set (GSE65391 and GSE49454 datasets). Compared with the blood samples of male normal subjects, the expression levels of PTGDS, IL11RA, STARD8, and S100A9 in the blood samples of male SLE patients were significantly changed (see Figure 4 Blood samples collected from Hainan Provincial People's Hospital also verified the significant changes in the expression levels of these four DEGs mRNA (see Figure 1 A- Figure 1 D), further demonstrated that PTGDS, IL11RA, STARD8, and S100A9 were significantly differentially expressed between male SLE patients and male normal subjects.

[0158] (3) GSE65391, GSE49454, and blood samples collected from Hainan Provincial People's Hospital were used to verify the diagnostic efficacy of DEGs

[0159] The matrix files of GSE65391 and GSE49454 were imported into RStudio to obtain the different expression levels of the four validated DEGs (PTGDS, IL11RA, STARD8, and S100A9). The sensitivity, specificity, cut-off value, and AUC value of the four genes and their combined models were calculated by the software. In the validation set (GSE65391+GSE49454), the diagnostic efficacy of PTGDS, IL11RA, STARD8, and / or S100A9 single detection indicators and the combined detection diagnostic model for male systemic lupus erythematosus are shown in Tables 3 and Figure 5 The results showed that any one or more of the markers PTGDS, IL11RA, STARD8 and / or S100A9 combined had good diagnostic accuracy for male systemic lupus erythematosus, especially the AUC value of the combination of IL11RA, STARD8, PTGDS and S100A9 was as high as 0.940, with sensitivity and specificity both higher than 84% (see Figure 5 The results of the combined diagnostic model (Figure 3 and Table 3) show high diagnostic accuracy, sensitivity, and specificity. The combined diagnostic model constructed using IL11RA, STARD8, PTGDS, and S100A9 significantly improves the diagnostic predictive ability of male SLE. Therefore, combined diagnostic markers can be used to improve the diagnostic efficacy of SLE in men. The combined diagnostic model (IL11RA, STARD8, PTGDS, and S100A9) for the early diagnosis of SLE in men, obtained through logistic regression analysis, is as follows:

[0160] Diagnostic model predicted value = 24.8812 + 1.6948 * PTGDS + 1.0869 * IL11RA - 2.2141 * STARD8 - 2.467 * S100A9;

[0161] Wherein, PTGDS, IL11RA, STARD8, and S100A9 represent the expression levels of PTGDS, IL11RA, STARD8, and S100A9 in the blood sample of the test subject, and * represents a multiplication sign;

[0162] The method for diagnosing and predicting whether a subject is a male systemic lupus erythematosus patient or the risk of developing male systemic lupus erythematosus is as follows: first, the expression levels of PTGDS, IL11RA, STARD8, and S100A9 in the blood sample of the subject are detected; then the detection values ​​are input into the above-mentioned diagnostic prediction model to calculate the diagnostic model prediction value. When the diagnostic model prediction value is ≤-0.195, the subject is judged to be a non-male systemic lupus erythematosus subject; when the diagnostic model prediction value is >-0.195, the subject is judged to be a male systemic lupus erythematosus patient or to have a high risk of developing male systemic lupus erythematosus.

[0163] Table 3 Statistical results of the diagnostic efficacy of four overlapping hub genes (PTGDS, IL11RA, STARD8, S100A9) as diagnostic markers for male SLE in the validation set

[0164]

[0165] Diagnostic model prediction value Combination model =24.8812+1.6948*PTGDS+1.0869*IL11RA-2.2141*STARD8-2.467*S100A9

[0166] The above embodiments are only provided for understanding the method and core concept of the present invention. It should be noted that, without departing from the principles of the present invention, a number of improvements and modifications may be made to the present invention by a person skilled in the art, and such improvements and modifications shall fall within the scope of protection of the claims of the present invention. Sequence Listing <110> Hainan Provincial People's Hospital <120> Early diagnostic markers for male systemic lupus erythematosus and related products and uses <141> 2022-05-20 <160> 10 <170> SIPOSequenceListing 1.0 <210> 1 <211> twenty one <212> DNA <213> Artificial Sequence <400> 1 caaccgggaa ggaaatgaat g 21 <210> 2 <211> 19 <212> DNA <213> Artificial Sequence <400> 2 gcccaatacg accaaatca 19 <210> 3 <211> 20 <212> DNA <213> Artificial Sequence <400> 3 catgacggaa caataggact 20 <210> 4 <211> 20 <212> DNA <213> Artificial Sequence <400> 4 gacttgcttc cggagtttat 20 <210> 5 <211> 20 <212> DNA <213> Artificial Sequence <400> 5 cggattaatg tgactgaggt 20 <210> 6 <211> 20 <212> DNA <213> Artificial Sequence <400> 6 ggtaacctgg tactgactct 20 <210> 7 <211> 20 <212> DNA <213> Artificial Sequence <400> 7 aagcaagcag aatgaagact 20 <210> 8 <211> 20 <212> DNA <213> Artificial Sequence <400> 8 cataggagac cagcacttac 20 <210> 9 <211> 20 <212> DNA <213> Artificial Sequence <400> 9 ccttccacca atactctgtg 20 <210> 10 <211> twenty one <212> DNA <213> Artificial Sequence <400> 10 ccatgatgtg ttctatgacc t 21

Claims

1. Use of reagents for detecting the expression levels of IL11RA, STARD8, PTGDS, and S100A9 in a sample in the preparation of a product for early diagnosis and / or prediction of systemic lupus erythematosus in men.

2. The use according to claim 1, characterized in that The reagents include reagents for detecting the expression levels of IL11RA, STARD8, PTGDS and S100A9 mRNA in a sample, and reagents for detecting the expression levels of IL11RA, STARD8, PTGDS and S100A9 proteins in a sample.

3. The use according to claim 2, characterized in that The reagent is selected from the following group: (1) Primers specifically amplifying IL11RA, STARD8, PTGDS, and S100A9; (2) probes that specifically recognize IL11RA, STARD8, PTGDS, and S100A9; (3) Binders that specifically bind to proteins encoded by IL11RA, STARD8, PTGDS, and S100A9.

4. The use according to claim 3, characterized in that The sequences of the primers for specifically amplifying IL11RA, STARD8, PTGDS and S100A9 are shown in SEQ ID NO: 5-SEQ ID NO: 6, SEQ ID NO: 7-SEQ ID NO: 8, SEQ ID NO: 3-SEQ ID NO: 4 and SEQ ID NO: 9-SEQ ID NO: 10, respectively.

5. The use according to claim 3, characterized in that The binding agent that specifically binds to proteins encoded by IL11RA, STARD8, PTGDS, and S100A9 includes antibodies that specifically bind to proteins encoded by IL11RA, STARD8, PTGDS, and S100A9.

6. The use according to claim 1, characterized in that The sample is tissue.

7. The use according to claim 1, characterized in that The sample is blood.

8. A diagnostic prediction model for early diagnosis and / or prediction of male systemic lupus erythematosus, characterized in that: The diagnostic prediction model includes the following markers: IL11RA, STARD8, PTGDS, and S100A9; The diagnostic prediction model uses the following regression equation to calculate the diagnostic model prediction value: Diagnostic model prediction value = 24.8812 + 1.6948 * PTGDS + 1.0869 * IL11RA - 2.2141 * STARD8 - 2.467 * S100A9; Among them, PTGDS, IL11RA, STARD8, and S100A9 represent the expression levels of PTGDS, IL11RA, STARD8, and S100A9 in the blood samples of the tested subjects; When the predicted value of the diagnostic model is ≤-0.195, the subject is judged to be a non-male systemic lupus erythematosus patient; when the predicted value of the diagnostic model is >-0.195, the subject is judged to be a male systemic lupus erythematosus patient or has a high risk of developing male systemic lupus erythematosus.

9. A system or device for early diagnosis and / or prognosis of male systemic lupus erythematosus, characterized in that: The system or device comprises: (1) A data acquisition module for acquiring expression profile data of IL11RA, STARD8, PTGDS, and S100A9 in samples of test subjects; (2) a diagnosis prediction module, configured to provide the expression profile data of IL11RA, STARD8, PTGDS, and S100A9 obtained by the data acquisition module as input data to a trained diagnosis prediction model, wherein the diagnosis prediction model is trained to perform a diagnosis prediction on the subject based on the expression profile data; (3) a diagnosis prediction result acquisition module, used to obtain the output result of the diagnosis prediction model in the diagnosis prediction module to obtain the diagnosis prediction result of the subject; The diagnostic prediction model is the diagnostic prediction model described in claim 8; When the predicted value of the diagnostic model is ≤-0.195, the subject is judged to be a non-male systemic lupus erythematosus patient; when the predicted value of the diagnostic model is >-0.195, the subject is judged to be a male systemic lupus erythematosus patient or has a high risk of developing male systemic lupus erythematosus.

10. A computer-readable storage medium, characterized in that The computer-readable storage medium includes a stored computer program, and when the program is executed, the following method is implemented: Obtaining expression profile data of IL11RA, STARD8, PTGDS, and S100A9 in samples from test subjects; providing the expression profile data of IL11RA, STARD8, PTGDS and S100A9 obtained by the data acquisition module as input data to the diagnosis prediction model; Outputting the subject's diagnostic prediction results; The diagnostic prediction model is the diagnostic prediction model described in claim 8; When the predicted value of the diagnostic model is ≤-0.195, the subject is judged to be a non-male systemic lupus erythematosus subject; When the predicted value of the diagnostic model is greater than -0.195, it is determined that the subject is a male systemic lupus erythematosus patient or has a high risk of developing male systemic lupus erythematosus.

11. Use of reagents for detecting the expression levels of IL11RA, STARD8, PTGDS, and S100A9 in constructing a system or device for early diagnosis and / or prediction of systemic lupus erythematosus in men.

12. Use of a reagent for detecting the expression levels of IL11RA, STARD8, PTGDS and S100A9 in constructing the computer-readable storage medium according to claim 10.

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